title: Restoration of renal responsiveness to atrial natriuretic peptide in experimental nephrotic syndrome by albumin infusion.
abstract: BACKGROUND
  The natriuretic/diuretic response to atrial natriuretic peptide (ANP), an important regulator of water and Na(+) balance, is markedly attenuated in nephrotic syndrome (NS). It has been suggested that the diminished renal responsiveness to ANP may contribute to the pathogenesis of salt retention and edema formation in NS. However, the mechanisms underlying the renal hyporesponsiveness to ANP remain largely unknown.
  
  
  METHODS
  The acute effects of exogenous infusion of ANP (5 µg/kg + 10 µg/kg/h) were studied by clearance methodology in control rats, hypoalbuminemic rats with Adriamycin (ADR)-induced NS and in ADR-treated rats infused with hyperoncotic albumin sufficient to restore plasma albumin to normal levels.
  
  
  RESULTS
  Administration of ANP to control rats resulted in a significant increase in urinary flow rate, absolute rate of sodium excretion (+456%) and glomerular filtration rate (GFR). Mean arterial blood pressure decreased following infusion of the peptide. In the nephrotic rats, baseline GFR and Na(+) excretion were significantly lower than in the control animals, and the renal effects of ANP were markedly blunt compared to the control animals. In contrast, the hypotensive effect of ANP in the ADR-treated rats was largely preserved. Infusion of hyperoncotic albumin prior to ANP administration reversed the decrease in baseline GFR and Na(+) excretion and completely restored the renal effects of ANP in the nephrotic rats.
  
  
  CONCLUSIONS
  These findings indicate that renal hyporesponsiveness to ANP in rats with ADR-induced NS is a reversible phenomenon that appears to be of functional origin rather than reflecting permanent cellular damage.
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion, Israel.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
authors.forename: Irit
authors.initials: I
authors.lastname: Weissman
authors.forename: Tony
authors.initials: T
authors.lastname: Karram
authors.forename: Ilia
authors.initials: I
authors.lastname: Goltsman
authors.forename: Aaron
authors.initials: A
authors.lastname: Hoffman
authors.forename: Ori S
authors.initials: OS
authors.lastname: Better
authors.forename: Joseph
authors.initials: J
authors.lastname: Winaver
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced; D005919:Glomerular Filtration Rate; D006801:Humans; D007022:Hypotension / Q000378:metabolism; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009401:Nephrosis / Q000473:pathology; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012492:Salts; D012964:Sodium / Q000378:metabolism
chemical_list: D000418:Albumins; D012492:Salts; C472610:atrial natriuretic peptide, rat; C028426:hyperoncotic albumin; D004317:Doxorubicin; D009320:Atrial Natriuretic Factor; D007444:Inulin; D012964:Sodium; D012083:Renin